Membrane-Acting Lytic Peptides Abstract Membrane-acting peptides (lytic peptides) are a group of cationic peptides which have their primary target site on the cell membrane and can kill cells by causing cell lysis. Because of the action site of lytic peptides is the cell membrane, they are effective to drug resistance cells, and can kill drug sensitive and resistant cells indiscriminately. This unique character makes lytic peptides become very attractive for their potential applications in the treatment of drug resistance related diseases. However, real application of lytic peptides as dugs is being hindered by their extremely low stability and selectivity. In this proposal, we propose to develop novel membrane-acting lytic peptides with high stability and selectivity. Smart lytic peptides have the potential to be used as drugs in the treatment of various drug resistance related diseases including cancer and infections. Two specific aims of this project are to: i) design and synthesize novel membrane-acting lytic peptides; ii) evaluate the stability, selectivity, and cell lysis activity of these membrane-acting lytic peptides in vitro and in vivo. Membrane-Acting Lytic Peptides Narrative Widespread drug resistance poses a significant problem and is responsible for the failure of chemotherapy in common diseases including cancers and various infections. In this application, we propose to introduce drug delivery concept into lytic peptide design to develop novel lytic peptides with high stability and selectivity. The success of this project may greatly improve the treatment of drug resistance related diseases such as cancer, infections, and infection associated diseases. [unreadable] [unreadable] [unreadable]